CN109953997A - A kind of preparation method of tilmicosin micro-capsule preparation - Google Patents
A kind of preparation method of tilmicosin micro-capsule preparation Download PDFInfo
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- CN109953997A CN109953997A CN201910322948.1A CN201910322948A CN109953997A CN 109953997 A CN109953997 A CN 109953997A CN 201910322948 A CN201910322948 A CN 201910322948A CN 109953997 A CN109953997 A CN 109953997A
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- JTSDBFGMPLKDCD-XVFHVFLVSA-N tilmicosin Chemical compound O([C@@H]1[C@@H](C)[C@H](O)CC(=O)O[C@@H]([C@H](/C=C(\C)/C=C/C(=O)[C@H](C)C[C@@H]1CCN1C[C@H](C)C[C@H](C)C1)CO[C@H]1[C@@H]([C@H](OC)[C@H](O)[C@@H](C)O1)OC)CC)[C@@H]1O[C@H](C)[C@@H](O)[C@H](N(C)C)[C@H]1O JTSDBFGMPLKDCD-XVFHVFLVSA-N 0.000 title claims abstract description 38
- 229960000223 tilmicosin Drugs 0.000 title claims abstract description 38
- 238000002360 preparation method Methods 0.000 title claims abstract description 33
- 239000003094 microcapsule Substances 0.000 title claims abstract description 18
- 239000003814 drug Substances 0.000 claims abstract description 11
- 238000003756 stirring Methods 0.000 claims abstract description 8
- 239000000126 substance Substances 0.000 claims abstract description 6
- 238000001035 drying Methods 0.000 claims abstract description 5
- 238000002844 melting Methods 0.000 claims abstract description 5
- 230000008018 melting Effects 0.000 claims abstract description 5
- 238000007711 solidification Methods 0.000 claims abstract description 5
- 230000008023 solidification Effects 0.000 claims abstract description 5
- 239000003945 anionic surfactant Substances 0.000 claims abstract description 4
- 238000001816 cooling Methods 0.000 claims abstract description 4
- 229910000831 Steel Inorganic materials 0.000 claims abstract description 3
- 238000010438 heat treatment Methods 0.000 claims abstract description 3
- 229940093429 polyethylene glycol 6000 Drugs 0.000 claims abstract description 3
- 239000010959 steel Substances 0.000 claims abstract description 3
- 239000003643 water by type Substances 0.000 claims abstract description 3
- RCEAADKTGXTDOA-UHFFFAOYSA-N OS(O)(=O)=O.CCCCCCCCCCCC[Na] Chemical group OS(O)(=O)=O.CCCCCCCCCCCC[Na] RCEAADKTGXTDOA-UHFFFAOYSA-N 0.000 claims description 5
- 239000003795 chemical substances by application Substances 0.000 claims description 2
- 230000003213 activating effect Effects 0.000 claims 1
- 125000000129 anionic group Chemical group 0.000 claims 1
- 238000000034 method Methods 0.000 abstract description 10
- 239000007962 solid dispersion Substances 0.000 abstract description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 abstract description 8
- 201000010099 disease Diseases 0.000 abstract description 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 5
- 235000019658 bitter taste Nutrition 0.000 abstract description 4
- 238000009360 aquaculture Methods 0.000 abstract description 2
- 244000144974 aquaculture Species 0.000 abstract description 2
- 239000003651 drinking water Substances 0.000 abstract description 2
- 235000020188 drinking water Nutrition 0.000 abstract description 2
- MTHSVFCYNBDYFN-UHFFFAOYSA-N diethylene glycol Chemical compound OCCOCCO MTHSVFCYNBDYFN-UHFFFAOYSA-N 0.000 description 9
- 238000004090 dissolution Methods 0.000 description 5
- 229940079593 drug Drugs 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 239000000243 solution Substances 0.000 description 4
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 230000006872 improvement Effects 0.000 description 3
- 238000002156 mixing Methods 0.000 description 3
- 238000012545 processing Methods 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 230000008685 targeting Effects 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 2
- 241000204031 Mycoplasma Species 0.000 description 2
- 239000008118 PEG 6000 Substances 0.000 description 2
- 229920002584 Polyethylene Glycol 6000 Polymers 0.000 description 2
- 229930194936 Tylosin Natural products 0.000 description 2
- 239000004182 Tylosin Substances 0.000 description 2
- 238000013461 design Methods 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 239000002609 medium Substances 0.000 description 2
- 239000000155 melt Substances 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 208000023504 respiratory system disease Diseases 0.000 description 2
- 208000011580 syndromic disease Diseases 0.000 description 2
- WBPYTXDJUQJLPQ-VMXQISHHSA-N tylosin Chemical compound O([C@@H]1[C@@H](C)O[C@H]([C@@H]([C@H]1N(C)C)O)O[C@@H]1[C@@H](C)[C@H](O)CC(=O)O[C@@H]([C@H](/C=C(\C)/C=C/C(=O)[C@H](C)C[C@@H]1CC=O)CO[C@H]1[C@@H]([C@H](OC)[C@H](O)[C@@H](C)O1)OC)CC)[C@H]1C[C@@](C)(O)[C@@H](O)[C@H](C)O1 WBPYTXDJUQJLPQ-VMXQISHHSA-N 0.000 description 2
- 229960004059 tylosin Drugs 0.000 description 2
- 235000019375 tylosin Nutrition 0.000 description 2
- 241000186046 Actinomyces Species 0.000 description 1
- 208000030090 Acute Disease Diseases 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 206010059866 Drug resistance Diseases 0.000 description 1
- 206010013786 Dry skin Diseases 0.000 description 1
- 241000192125 Firmicutes Species 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 241000606860 Pasteurella Species 0.000 description 1
- 206010035664 Pneumonia Diseases 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 230000006978 adaptation Effects 0.000 description 1
- 210000001132 alveolar macrophage Anatomy 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 230000004596 appetite loss Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 238000009395 breeding Methods 0.000 description 1
- 230000001488 breeding effect Effects 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 239000013065 commercial product Substances 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 239000006184 cosolvent Substances 0.000 description 1
- 239000003405 delayed action preparation Substances 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 239000012738 dissolution medium Substances 0.000 description 1
- 238000007922 dissolution test Methods 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 238000001647 drug administration Methods 0.000 description 1
- 239000002702 enteric coating Substances 0.000 description 1
- 238000009505 enteric coating Methods 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 210000004211 gastric acid Anatomy 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 230000007794 irritation Effects 0.000 description 1
- 150000002596 lactones Chemical class 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000007791 liquid phase Substances 0.000 description 1
- 244000144972 livestock Species 0.000 description 1
- 235000021266 loss of appetite Nutrition 0.000 description 1
- 208000019017 loss of appetite Diseases 0.000 description 1
- -1 microballoon Substances 0.000 description 1
- 239000012982 microporous membrane Substances 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 210000004400 mucous membrane Anatomy 0.000 description 1
- 239000007908 nanoemulsion Substances 0.000 description 1
- 238000007500 overflow downdraw method Methods 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 201000006509 pleuropneumonia Diseases 0.000 description 1
- 235000019353 potassium silicate Nutrition 0.000 description 1
- 244000144977 poultry Species 0.000 description 1
- 230000002685 pulmonary effect Effects 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 230000029058 respiratory gaseous exchange Effects 0.000 description 1
- 238000005070 sampling Methods 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 238000007789 sealing Methods 0.000 description 1
- NTHWMYGWWRZVTN-UHFFFAOYSA-N sodium silicate Chemical compound [Na+].[Na+].[O-][Si]([O-])=O NTHWMYGWWRZVTN-UHFFFAOYSA-N 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 235000013599 spices Nutrition 0.000 description 1
- 229910001220 stainless steel Inorganic materials 0.000 description 1
- 239000010935 stainless steel Substances 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 238000002626 targeted therapy Methods 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7052—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
- A61K31/706—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Molecular Biology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses a kind of preparation methods of tilmicosin micro-capsule preparation, it is comprised the technical steps that: taking polyethylene glycol 6000 is used as carrier, the heating in 60 DEG C of waters bath with thermostatic control, which is added after the anionic surfactant of carrier quality 1~3%, makes its all melting, Tilmicosin bulk pharmaceutical chemicals are added while stirring again to melting completely, medicine is carried than being 1:2 by mass, it is poured into rapidly in the rustless steel container of pre-cooling afterwards, it is sequentially placed into solidification in -20 DEG C of refrigerators, drying in 35~40 DEG C of drying boxes, it most ground afterwards, cross 80 meshes, obtain finished product.The present invention solves the problems, such as that existing tilmicosin micro-capsule preparation not soluble in water, bitter, bioavilability are low, bitter taste can be covered, be dissolved in water by being prepared into using solid dispersions technique, the high tilmicosin micro-capsule preparation of bioavilability, it facilitates drinking water administration, disease can be treated, in time so as to bring bigger convenience and interests to aquaculture.
Description
Technical field
The present invention relates to biomedicine field, in particular to a kind of preparation method of tilmicosin micro-capsule preparation.
Background technique
Tilmicosin is a kind of Novel macrocyclic lactone livestock and poultry dedicated antibiotic semi-synthetic by tylosin, to gram
Positive bacteria and part Gram-negative bacteria, mycoplasma, conveyor screw etc. have good inhibiting effect, to pleuropneumonia actinomyces,
Pasteurella has antibacterial activity more stronger than tylosin, with clinical common antibiotics without drug resistance of reporting to the leadship after accomplishing a task.It is clinically main
For the mazoitis of animal respiratory disease and lactating mammal, especially in treatment porcine respiratory disease syndrome and pig breeding and breathing
Significant superiority is shown when syndrome.But Tilmicosin has certain irritation, Tilmicosin mainly take it is for oral administration and
Injected s.c. administration, is especially used with caution drug administration by injection to pig, causes it to promote and apply in veterinary clinic and be restricted.
Tilmicosin extremely difficult dissolution in water has stronger bitter taste, takes orally, bioavilability irritating to stomach mucous membrane
Lower, primary formulation is its phosphate in the market, is easily destroyed by gastric acid after for oral administration, is absorbed not exclusively, bioavilability is low, in vivo
Half-life short.Main in veterinary clinic to be administered by spice, easy loss of appetite when due to animal suffering from disease cannot be played and be controlled in time
Treat the effect of disease.Therefore, the water solubility, bioavilability, targeting for improving Tilmicosin extend its partly declining in vivo
Phase heightens the effect of a treatment, it has also become one of the important topic of the efficient research on utilization of current Tilmicosin.
In recent years, micro-capsule, microballoon, pellet, nano-emulsion, enteric coating particle, inclusion compound, liposome, solid dispersions
Etc. new technologies applied in the research of tilmicosin micro-capsule preparation, to a certain extent, improve the solubility of drug, cover
The bitter taste of Tilmicosin, and there is sustained release, the effect of targeting.But Tilmicosin targeting is in pulmonary alveolar macrophage,
The effect of targeted therapy is itself had, and for some acute diseases, sustained release preparation can not play the role for the treatment of in time, greatly
Portion of techniques needs to be added organic reagent, and dosage is larger, higher cost, and is difficult to eliminate sometimes, pollutes environment, currently, this
A little new agent technologies are not applied in actual production also.
Summary of the invention
It is an object of the invention in view of the above shortcomings of the prior art, provide a kind of preparation side of tilmicosin micro-capsule preparation
Method, the Tilmicosin solid dispersions drugloading rate being prepared into is high, can be quickly dissolved in water, has to timely treatment disease important
Clinical value.
The technical solution used in the present invention is: a kind of preparation method of tilmicosin micro-capsule preparation comprising following technique step
Rapid: taking polyethylene glycol 6000 is used as carrier, is added after the anionic surfactant of carrier quality 1~3% in 60 DEG C of thermostatted waters
Heating melts it all in bath, then Tilmicosin bulk pharmaceutical chemicals are added while stirring to melting completely, and medicine load ratio is by mass
1:2 is poured into rapidly afterwards in the rustless steel container of pre-cooling, is sequentially placed into solidification in -20 DEG C of refrigerators, is done in 35~40 DEG C of drying boxes
It is dry, it most ground afterwards, cross 80 meshes, obtain finished product.
The present invention prepares Tilmicosin solid dispersions using fusion method, it is not necessary that the cosolvents such as organic reagent are added, distinguishes
Tilmicosin micro-capsule preparation is prepared in traditional solvent method, with more safe and pollution-free, preparation method is simple, it is extensive to be conducive to
The advantages of industrialized production.
As a further improvement of the foregoing solution, the anionic surfactant is lauryl sodium sulfate.Specifically,
Lauryl sodium sulfate has preferable dispersion performance and dissolution assistant effect, is scattered in Tilmicosin uniformly in carrier, is formed
Disperse uniform solid dispersions, melts Tilmicosin solid dispersions faster.
As a further improvement of the foregoing solution, the mixing time of the stirring is 2h.
As a further improvement of the foregoing solution, the cured curing time is 12h.
The beneficial effects of the present invention are: the present invention solves existing tilmicosin micro-capsule preparation not soluble in water, bitter, biological utilisation
Low problem is spent, is prepared into using solid dispersions technique and can cover bitter taste, be dissolved in water, the high Tilmicosin of bioavilability
Preparation facilitates drinking water administration, can treat disease in time, so as to bring bigger convenience and interests to aquaculture.
Specific embodiment
The present invention is specifically described below with reference to embodiment, in order to technical field personnel to of the invention
Understand.It is necessary to it is emphasized that embodiment is only intended to, the present invention will be further described herein, should not be understood as to this
The limitation of invention protection scope, fields person skilled in the art, the non-intrinsically safe that the present invention is made according to foregoing invention content
The modifications and adaptations of property, should still fall within protection scope of the present invention.Mentioned raw materials following simultaneously are unspecified, are
Commercial product；The processing step or preparation method not referred in detail be processing step known to a person skilled in the art or
Preparation method.
Embodiment
1, experiment reagent and drug
Tilmicosin bulk pharmaceutical chemicals, PEG6000, lauryl sodium sulfate
2, solid dispersions are prepared
It takes carrier PEG6000 to be placed in a beaker, the lauryl sodium sulfate of carrier quality 1~3% is added, 60 DEG C of water-baths add
Heat makes its melting, and Tilmicosin bulk pharmaceutical chemicals are added, stirring while adding, is melted into Tilmicosin bulk pharmaceutical chemicals in medium completely, continues
It stirs to certain time.Beaker is taken out from water-bath, is poured into rapidly in the stainless steel pallet of pre-cooling, is then transferred to -20 DEG C
Refrigerator solidification, taking-up set 35~40 DEG C of air dry ovens dryings, take out, grind from pallet, cross 80 meshes, sealing is kept in dark place
Obtain tilmicosin micro-capsule preparation finished product of the invention.
3, screening technique
Their Dissolution Test in vitro: one annex of " Republic of China Veterinary Pharmacopoeia " version in 2015,160 second method (paddle is pressed
Method) testing drug dissolution rate.
Take Tilmicosin raw medicine, tilmicosin micro-capsule preparation finished product of the invention appropriate (being equivalent to Tilmicosin raw medicine 100mg),
Dissolution medium is the distilled water 900mL of degassed processing, 37 DEG C of temperature, revolving speed 100r/min, respectively with 2,5,10,15,20,
30,45 and 60min quantitative sampling 5mL, while equivalent equality of temperature medium 5mL is supplemented, through 0.22 μm of filtering with microporous membrane, efficient liquid phase
Chromatography measures peak area respectively, calculates the concentration of different time sample liquid, seeks the accumulation dissolution rate for calculating drug.
4, preparation process screens (orthogonal test)
1 Orthogonal Experiment and Design factor of table and water-glass
| Horizontal factor | Medicine carries ratio | Mixing time (h) | Curing time (h) |
| 1 | 1∶1 | 1 | 4 |
| 2 | 1∶2 | 2 | 8 |
| 3 | 1∶3 | 3 | 12 |
2 orthogonal test designs table of table
Dissolution rate table (%) is accumulated in 3 1h of table
| 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | 9 | |
| 2min | 17.09 | 15.56 | 17.26 | 17.03 | 16.71 | 16.57 | 28.32 | 20.68 | 22.61 |
| 5min | 32.50 | 28.86 | 29.27 | 30.01 | 31.52 | 29.97 | 46.71 | 37.27 | 36.65 |
| 10min | 49.57 | 45.33 | 46.45 | 46.47 | 47.75 | 46.03 | 63.64 | 55.01 | 54.07 |
| 15min | 60.01 | 57.48 | 59.41 | 60.46 | 59.18 | 57.81 | 73.13 | 66.17 | 64.79 |
| 20min | 68.23 | 65.60 | 68.43 | 68.52 | 67.24 | 65.95 | 79.57 | 74.16 | 73.03 |
| 30min | 78.06 | 78.25 | 79.15 | 80.45 | 77.90 | 77.30 | 85.83 | 82.70 | 81.78 |
| 45min | 84.75 | 84.10 | 86.36 | 88.79 | 85.71 | 85.51 | 88.76 | 88.35 | 86.86 |
| 60min | 89.69 | 90.38 | 94.28 | 95.10 | 94.85 | 94.33 | 91.69 | 94.66 | 89.86 |
It is analyzed according to orthogonal experiments, A2> A3> A1, B2> B3> B1, C3> C1> C2, optimal preparation process is
A2B2C3, i.e. medicine load is than 1:2, mixing time 2h, curing time 12h.
Above-described embodiment is the preferred embodiment of the present invention, all with similar technique of the invention and made equivalence changes,
It should belong to protection category of the invention.
Claims (4)
1. a kind of preparation method of tilmicosin micro-capsule preparation, it is characterised in that comprise the technical steps that: taking polyethylene glycol 6000 is made
For carrier, the heating in 60 DEG C of waters bath with thermostatic control, which is added after the anionic surfactant of carrier quality 1~3%, keeps it all molten
Melt, then Tilmicosin bulk pharmaceutical chemicals are added while stirring to melting completely, medicine is carried than being 1:2 by mass, pours into pre-cooling rapidly afterwards
Rustless steel container in, be sequentially placed into -20 DEG C of refrigerators solidification, dry in 35~40 DEG C of drying boxes, most ground afterwards, cross 80 mesh
Sieve, obtains finished product.
2. a kind of preparation method of tilmicosin micro-capsule preparation according to claim 1, it is characterised in that: the anionic surface
Activating agent is lauryl sodium sulfate.
3. a kind of preparation method of tilmicosin micro-capsule preparation according to claim 1, it is characterised in that: the stirring of the stirring
Time is 2h.
4. a kind of preparation method of tilmicosin micro-capsule preparation according to claim 1, it is characterised in that: the cured solidification
Time is 12h.
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|---|---|---|---|
| CN201910322948.1A CN109953997B (en) | 2019-04-22 | 2019-04-22 | Preparation method of tilmicosin preparation |
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|---|---|---|---|
| CN201910322948.1A CN109953997B (en) | 2019-04-22 | 2019-04-22 | Preparation method of tilmicosin preparation |
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| CN109953997A true CN109953997A (en) | 2019-07-02 |
| CN109953997B CN109953997B (en) | 2021-06-29 |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111407728A (en) * | 2020-04-16 | 2020-07-14 | 重庆市畜牧科学院 | Tilmicosin enteric solid dispersion and preparation method and application thereof |
| CN113712988A (en) * | 2021-08-17 | 2021-11-30 | 塔里木大学 | Quercetin-tilmicosin polymer nanoparticles as well as preparation method and application thereof |
| CN115645376A (en) * | 2022-10-26 | 2023-01-31 | 山东德州神牛药业有限公司 | Tilmicosin efficient double-layer coated pellet and preparation method thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN111407728A (en) * | 2020-04-16 | 2020-07-14 | 重庆市畜牧科学院 | Tilmicosin enteric solid dispersion and preparation method and application thereof |
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| CN115645376A (en) * | 2022-10-26 | 2023-01-31 | 山东德州神牛药业有限公司 | Tilmicosin efficient double-layer coated pellet and preparation method thereof |
| CN115645376B (en) * | 2022-10-26 | 2023-10-31 | 山东德州神牛药业有限公司 | Efficient double-layer coated tilmicosin pellets and preparation method thereof |
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Effective date of registration: 20231026 Address after: 528300 Guangdong Province, Foshan city Shunde District Daliang Honggang Industrial Zone Patentee after: GUANGDONG YANGBLE BIOPHARMACEUTICALS Co.,Ltd. Address before: No.33, Guangyun Road, Nanhai District, Foshan City, Guangdong Province Patentee before: FOSHAN University |